Fingolimod, chemically 2-amino-2-[2-(4-octylphenyl)ethyl-]propane-1,3-diol, compound of formula (I), is an S1P receptor agonist. It has been approved for treating multiple sclerosis in USA (trade name GILENYA™) and Russia in 2010 and in Europe, Canada and Australia in 2011.

The recommended dose of GILENYA™ is 500 micrograms orally once daily. Fingolimod doses higher than 0.5 mg are associated with a greater incidence of adverse reactions without additional benefit. Fingolimod is a very potent drug and therefore individual units of a dosage form such as capsule or tablets must contain the desired dose of 500 micrograms. It is essential that a low quantity of fingolimod be uniformly distributed in the pharmaceutical excipients that are then filled into capsules or compressed into tablets. Moreover, the fingolimod in the composition must be chemically stable and should be released rapidly from the composition at a desirable dissolution rate. GILENYA™ when tested in of 0.1 N Hydrochloric acid with 1% (w/v) Tween 80 using USP Type II Apparatus rotating at 75 rpm, provides desirable dissolution of more than 80% in 45 minutes.
U.S. Pat. No. 8,324,283 claimed solid pharmaceutical composition for oral administration comprising a S1P receptor agonist such as Fingolimod and a sugar alcohol. The compositions of the invention were to possess good handling physicochemical and storage properties and in particular they provide a high level of uniformity of the distribution of the S1P receptor agonist.
PCT publication, WO2011131368 A2 provided a method of preparing an intermediate comprising (a) fingolimod and (b) one or more pharmaceutically acceptable excipients, comprising the steps of: (i) optionally mixing (a) fingolimod and (b) the excipient or the plurality of excipients, (ii) jointly comminuting (a) fingolimod and (b) the one or more excipients into intermediate particles such that 90 percent by volume of all the resulting intermediate particles have a particle size of less than 250 μms and greater than 0.6 μms. This PCT patent publication explains the invention that the intermediates in the particle size range specified above are particularly advantageous for further use or further processing and that, as a result, a uniform content of active agent, especially in the oral dosage forms based on them, can be achieved. The process taught by the application is well known in the art and is referred to as geometric mixing. We found that the method does not give a high degree of uniformity. Another prior art PCT publication, WO2011131370 A1 provides a method of preparing an intermediate, comprising melt processing (i) fingolimod or a pharmaceutically acceptable salt thereof, with (ii) a matrix former.